Recruitment of highly cytotoxic CD8+ T cell receptors in mild SARS-CoV-2 infection

• Published in: Cell reports (Cambridge) 2022-01, Vol.38 (2), p.110214-110214, Article 110214
• Main Authors: Wagner, Karolin I., Mateyka, Laura M., Jarosch, Sebastian, Grass, Vincent, Weber, Simone, Schober, Kilian, Hammel, Monika, Burrell, Teresa, Kalali, Behnam, Poppert, Holger, Beyer, Henriette, Schambeck, Sophia, Holdenrieder, Stefan, Strötges-Achatz, Andrea, Haselmann, Verena, Neumaier, Michael, Erber, Johanna, Priller, Alina, Yazici, Sarah, Roggendorf, Hedwig, Odendahl, Marcus, Tonn, Torsten, Dick, Andrea, Witter, Klaus, Mijočević, Hrvoje, Protzer, Ulrike, Knolle, Percy A., Pichlmair, Andreas, Crowell, Claudia S., Gerhard, Markus, D’Ippolito, Elvira, Busch, Dirk H.
• Format: Article
• Language: English
• Subjects: Adult; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; Cells, Cultured; COVID-19 - immunology; Cross Reactions - immunology; cytotoxic T cells; Epitopes, T-Lymphocyte - immunology; Female; Humans; Immunodominant Epitopes - immunology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Male; mild COVID-19; Receptors, Antigen, T-Cell - immunology; SARS-CoV-2 - immunology; SARS-CoV-2 infection; scRNA sequencing; Spike Glycoprotein, Coronavirus - immunology; T cell immunity; T cell receptor; T-Lymphocytes, Cytotoxic - immunology; TCR engineering; TCR identification
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.110214

T cell immunity is crucial for control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been studied widely on a quantitative level. However, the quality of responses, in particular of CD8+ T cells, has only been investigated marginally so far. Here, we isolate T cell receptor (TCR) repertoires specific for immunodominant SARS-CoV-2 epitopes restricted to common human Leukocyte antigen (HLA) class I molecules in convalescent individuals. SARS-CoV-2-specific CD8+ T cells are detected up to 12 months after infection. TCR repertoires are diverse, with heterogeneous functional avidity and cytotoxicity toward virus-infected cells, as demonstrated for TCR-engineered T cells. High TCR functionality correlates with gene signatures that, remarkably, could be retrieved for each epitope:HLA combination analyzed. Overall, our data demonstrate that polyclonal and highly functional CD8+ TCRs—classic features of protective immunity—are recruited upon mild SARS-CoV-2 infection, providing tools to assess the quality of and potentially restore functional CD8+ T cell immunity. [Display omitted] •SARS-CoV-2-specific CD8+ T cells are detectable up to 12 months after infection•scRNA sequencing reveals polyclonal CD8+ T cells with variable functionalities•High-avidity CD8+ T cells engineered with SARS-CoV-2-specific TCRs are cytotoxic•Single cell signature for highly functional SARS-CoV-2-specific CD8+ T cells Wagner et al. detect CD8+ T cell responses to diverse immunodominant SARS-CoV-2-specific epitopes. scRNA sequencing of epitope-responsive CD8+ T cells reveals a polyclonal T cell receptor repertoire. State-of-the-art TCR re-expression confirms a highly specific and functional T cell response in convalescent mild COVID-19.